Developmental Potential for Endomorphin Opioidmimetic Drugs

  title={Developmental Potential for Endomorphin Opioidmimetic Drugs},
  author={Y. Okada and Y. Tsuda and S. Salvadori and L. Lazarus},
  journal={International Journal of Medicinal Chemistry},
Morphine, which is agonist for μ-opioid receptors, has been used as an anti-pain drug for millennia. The opiate antagonists, naloxone and naltrexone, derived from morphine, were employed for drug addiction and alcohol abuse. However, these exogenous agonists and antagonists exhibit numerous and unacceptable side effects. Of the endogenous opioid peptides, endomorphin(EM)-1 and endomorphin(EM)-2 with their high μ-receptor affinity and exceptionally high selectivity relative to δ- and κ-receptors… Expand
3 Citations
An Engineered Endomorphin-2 Gene for Morphine Withdrawal Syndrome
After administration of the adenovirus in central nervous system, a sustained increase of EM2 level in the cerebral spinal fluid (CSF) was observed along with a reduction of morphine withdrawal syndrome, suggesting that the engineered EM2 gene delivered to thecentral nervous system could be a novel therapeutics for withdrawal syndrome in opioid dependent subjects. Expand
Antilipase activity guided fractionation of Vinca major
Abstract Methanolic extract of flowers of Vinca major (VFE) reduced the activity of porcine pancreatic lipase (PPL) which was reported in our previous study. To identify the antilipase molecule(s) inExpand
Evolution of thermo-physical properties of Akuama (picralima nitida) seed and antioxidants retention capacity during hot air drying
Interest in picralima nitida is growing over the years because of its therapeutic application in human and animal medicine. In many countries the dried seed is compounded and sold as drugs but thereExpand


[N-Allyl-Dmt1]-Endomorphins Are μ-Opioid Receptor Antagonists Lacking Inverse Agonist Properties
[N-Allyl-Dmt1]-endomorphin-1 and -2 ([N-allyl-Dmt1]-EM-1 and -2) are new selective μ-opioid receptor antagonists obtained by N-alkylation with an allyl group on the amino terminus ofExpand
A potent and selective endogenous agonist for the µ-opiate receptor
Peptides have been identified in mammalian brain that are considered to be endogenous agonists for the δ (enkephalins) and κ (dynorphins) opiate receptors, but none has been found to have anyExpand
Design of δ-opioid peptide antagonists for emerging drug applications
Abstract The need for δ-receptor-selective opioid antagonists has led to their development based on structure–activity relationships of δ- and μ-opioid agonists. The unusual amino acidExpand
Development of potent mu-opioid receptor ligands using unique tyrosine analogues of endomorphin-2.
The active profile of the [Xaa(1)]EM-2 analogues indicated that significant modifications on the tyramine ring are possible while high biological activity is maintained. Expand
Development of Potent Bifunctional Endomorphin-2 Analogues with Mixed μ-/δ-Opioid Agonist and δ-Opioid Antagonist Properties
The C terminus of endomorphin-2 (EM-2) analogues (Tyr-Pro-Phe-NH-X) was modified with aromatic, heteroaromatic, or aliphatic groups (X = phenethyl,benzyl, phenyl, naphthyl, pyridyl, quinolyl,Expand
δ Opioidmimetic Antagonists: Prototypes for Designing a New Generation of Ultraselective Opioid Peptides
Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid δ antagonist naltrindole and have potential application as clinical and therapeutic compounds. Expand
Modulation of endomorphin-2-induced analgesia by dipeptidyl peptidase IV
The present study found that endomorphin-2 was degraded approximately twice as fast than the chromogenic substrate, Ala-Pro-2naphthylamide, by dipeptidyl peptidase IV, whereas d-Pro2-endomorph in- vivo was totally resistant to this enzyme's action. Expand
Unique high-affinity synthetic mu-opioid receptor agonists with central- and systemic-mediated analgesia.
Unique opioid mimetic substances containing identical N-terminal aromatic residues separated by an unbranched alkyl chain containing two to eight methylene groups were developed and it appears that the bis-Dmt compounds indiscriminately act as both message and address domains. Expand
Endomorphin 2 analogues containing Dmp residue as an aromatic amino acid surrogate with high mu-opioid receptor affinity and selectivity.
Results suggested that the Dmp residue can mimic Tyr(1), which is one of the critical structural elements of opioid peptides. Expand
The novel micro-opioid receptor antagonist, [N-allyl-Dmt(1)]endomorphin-2, attenuates the enhancement of GABAergic neurotransmission by ethanol.
AIMS We investigated the effects of [N-allyl-Dmt(1)]endomorphin-2 (TL-319), a novel and highly potent micro-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABA(A)Expand